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The endocannabinoid system (ECS) represents the largest signaling system in humans, having more receptors than all other neurotransmitter systems, combined.

When ECS activity becomes abnormal, then the systems which rely on the ECS for regulation won’t receive the regulation they need, and will begin causing symptoms of disease. This phenomenon is known as endocannabinoid deficiency, and more research is conducted daily to learn how endocannabinoid deficiency could affect human health and disease.

What is the endocannabinoid system?

The endocannabinoid system is the homeostasis system of our body: it’s in charge of keeping everything else in harmony and balance.

The purpose of the ECS is still being uncovered, but the general consensus is that its role is to regulate the baseline activity levels of the central and peripheral nervous system, the immune system, the digestive system, and several other body systems.

The endocannabinoid system is comprised of three main parts:

Signaling molecules (endocannabinoids like 2-AG, anandamide, and several others);

The receptors that the signaling molecules act on (CB1, CB2, TRPV1, GPR-18, GPR-55, and several others), and;

The enzymes that produce and degrade the signaling molecules (MAGL, DAGL, FAAH, and others yet to be discovered).

The effect of the endocannabinoid system depends on which receptors are present in a given cell type, which endocannabinoids are activating those receptors, and how active the enzymes are that produce and degrade the endocannabinoids. All of these variables account for why the ECS performs such diverse roles throughout so many different body systems.

In general, the role of the ECS is to provide constant activation of endocannabinoid receptors. This continuous baseline activity, known as endocannabinoid tone, sets the baseline activity of the cell in which the activity is taking place. It also allows for both an increase, and a decrease, in activity levels. It’s like the difference between an on/off lightswitch and a dimmer switch. Most neurotransmitters are either on or off, but the ECS is able to finely-tune itself depending on the specific needs at that moment.

In brain cells, endocannabinoid tone determines the excitability of the neuron. In immune cells, it determines how aggressively the cell will produce an inflammatory response. In these examples, both too much and too little activity would cause health problems, and an intermediate range - known as homeostasis - is necessary to stay healthy.

What is endocannabinoid deficiency?

When the presence of endocannabinoids, their receptors, or their enzymes becomes too great or too minimal, then the system as a whole won’t produce the physiological - or “healthy” - effect that it usually produces. Instead, it will produce a pathological - or “unhealthy” - effect in the tissue that it regulates.

Dysregulation of the endocannabinoid system is highly correlated with secondary dysregulation of the various systems which are controlled or regulated by the endocannabinoid system, and this secondary dysregulation is now being considered as the potential root cause of many common conditions which currently have no known root cause.

Many conditions and disorders, from seasonal allergies to Parkinson’s disease, are at least partially caused by neurotransmitter deficiency. Deficiency can mean either too little or too much of a given neurotransmitter.

For example, increased levels of the neurotransmitter histamine can cause allergic reactions to non-toxic compounds (like tree pollen), while decreased levels of dopamine in Parkinson’s disease prevent the dopaminergic signalling required for voluntary movement to take place.

Similarly, abnormal levels of endocannabinoids or endocannabinoid receptors may be involved in many diverse conditions, which respond positively to cannabis treatment, and the root causes of which have not yet been discovered.

The term “endocannabinoid deficiency” was coined by Dr. Ethan Russo (medical advisor to Sativex and Epidiolex manufacturer GW Pharmaceuticals) back in 2000, and was fortified in 2004. Hundreds of in vivo (in the body) preclinical and animal studies show a significant correlation between altered endocannabinoid system levels and idiopathic conditions including fibromyalgia, migraine, irritable bowel syndrome, and several others which have at least the following four characteristics:

The conditions are largely idiopathic, meaning we don’t know the root cause;

The conditions have high rates of comorbidities, meaning they are rarely the patient’s only diagnosis;

The conditions do not respond well, if at all, to traditional pharmaceutical therapies, and;

The conditions do respond well to treatment with various forms of cannabis or cannabinoids.

If a condition meets these four criteria, then there’s a high likelihood that endocannabinoid deficiency is a partial cause.

Endocannabinoid deficiency is not yet well-known in the medical community, and only 13% of medical schools even mention the endocannabinoid system in their curricula. However, more research is not necessarily the answer to this problem. Extensive and well-established research already exists that proves that the endocannabinoid system is integrally involved in human health and disease. What needs to happen next is for doctors and healthcare professionals to begin making decisions based on current science, rather than what they learn in school decades ago.

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